Adenosine Therapeutics, LLC (ATL) is a biotechnology company started in Charlottesville, Virginia in 1999. ATL owns patents on the formulation and use of a family of potent and highly selective agonists of A2A adenosine receptors. One of these compounds, ATL146e, is a coronary vasodilator and has been developed (with the aid of SBIR funding) as a coronary artery imaging agent that has been licensed to Bristol Meyers Squibb exclusively for pharmacological imaging of coronary disease and is currently in phase I clinical trials. ATL146e and other agonists of A2A adenosine receptors exert powerful anti-inflammatory effects by actions on bone-marrow derived cells at doses far below those that are vasoactive. Dr. Fabio Cominelli and his colleagues in the University of Virginia (UVa) are experts in the study of inflammatory bowel diseases (IBD). They have found in rabbit models that ATL146e is profoundly protective against inflammation and injury that occurs as a result of ulcerative colitis. This is an SBIR-AT phase I proposal by ATL and UVa for the purpose of developing ATL146e and a second generation orally active compound as new therapies for the treatment of IBD. This concept will be tested in a relevant mouse model of IBD that has been well characterized by the Cominelli laboratory. The aims are: (1) to optimize drug dosing and timing; (2) determine if ATL146e can delay the onset of disease symptoms; (3) characterize a second generation orally active compound; (4) synthesize new compounds and radioactive analogs; and (5) determine the chemical properties, pharmacokinetics and biodistribution of drug candidates. There is a great need for improved therapies for IBD. Our goal is to begin clinical trials with a new drug for the treatment of IBD within two years and to develop a second generation compound within four years.